Microbiota-produced immune regulatory bile acid metabolites control central nervous system autoimmunity
Martina Antonini Cencicchio, Federico Montini, Vittoria Palmieri, Luca Massimino, Marta Lo Conte, Annamaria Finardi, Alessandra Mandelli, Francesco Asnicar, Radmila Pavlović, Denise Drago, Federica Ungaro, Annapaola Andolfo, Nicola Segata, Vittorio Martinelli, Roberto Furlan, Marika Falcone
Abstract
regulatory T (Treg) cell differentiation at the expense of Th17 cells. Here, we show that bacteria releasing enzymes responsible for secondary BAMs production are under-represented in the gut of MS patients, resulting in significantly reduced intestinal concentration of DCA and immune dysregulation with increased percentage of Th17 cells. We validated our human findings in a preclinical model of MS by showing that DCA/LCA administration prevents experimental autoimmune encephalomyelitis (EAE) by dampening Th17 cell differentiation and the effector phenotype of myelin-reactive T cells. Our data highlight the key role of immune regulatory BAMs for the prevention of central nervous system (CNS) autoimmunity.